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Stereotactic radiosurgery for IDH wild type glioblastoma: an international, multicenter study

Bunevicius, Adomas; Pikis, Stylianos; Kondziolka, Douglas; Patel, Dev N; Bernstein, Kenneth; Sulman, Erik P; Lee, Cheng-Chia; Yang, Huai-Che; Delabar, Violaine; Mathieu, David; Cifarelli, Christopher P; Arsanious, David E; Dahshan, Basem A; Weir, Joshua S; Speckter, Herwin; Mota, Angel; Tripathi, Manjul; Kumar, Narendra; Warnick, Ronald E; Peker, Selcuk; Samanci, Yavuz; Barnett, Gene; Hefnawi, Farid El; Al Sideiri, Ghusn; Sheehan, Jason
OBJECTIVE:Isocitrate dehydrogenase (IDH) mutation status is recommended used for diagnosis and prognostication of glioblastoma patients. We studied efficacy and safety of stereotactic radiosurgery (SRS) for patients with recurrent IDH-wt glioblastoma. METHODS:Consecutive patients treated with SRS for IDH-wt glioblastoma were pooled for this retrospective observational international multi-institutional study from institutions participating in the International Radiosurgery Research Foundation. RESULTS:) for IDH-wt glioblastoma. All patients had histories of surgery and chemotherapy with temozolomide, and 98% underwent fractionated radiation therapy. MGMT status was available for 42 patients, of which half of patients had MGMT mutant glioblastomas. During median post-SRS imaging follow-up of 6 months, 52% of patients experienced tumor progression. Median post-SRS progression free survival was 4 months. SRS prescription dose of > 14 Gy predicted longer progression free survival [HR 0.357 95% (0.164-0.777) p = 0.009]. Fifty-percent of patients died during post-SRS clinical follow-up that ranged from 1 to 33 months. SRS treatment volume of > 5 cc emerged as an independent predictor of shorter post-SRS overall survival [HR 2.802 95% CI (1.219-6.444) p = 0.02]. Adverse radiation events (ARE) suggestive of radiation necrosis were diagnosed in 6/55 (10%) patients and were managed conservatively in the majority of patients. CONCLUSIONS:SRS prescription dose of > 14 Gy is associated with longer progression free survival while tumor volume of > 5 cc is associated with shorter overall survival after SRS for IDH-wt glioblastomas. AREs are rare and are typically managed conservatively.
PMID: 34797526
ISSN: 1573-7373
CID: 5049702

Stereotactic radiosurgery for glioblastoma considering tumor genetic profiles: an international multicenter study

Bunevicius, Adomas; Pikis, Stylianos; Kondziolka, Douglas; Patel, Dev N; Bernstein, Kenneth; Sulman, Erik P; Lee, Cheng-Chia; Yang, Huai-Che; Delabar, Violaine; Mathieu, David; Cifarelli, Christopher P; Arsanious, David E; Dahshan, Basem A; Weir, Joshua S; Speckter, Herwin; Mota, Angel; Tripathi, Manjul; Kumar, Narendra; Warnick, Ronald E; Sheehan, Jason P
OBJECTIVE:Molecular profiles, such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) methylation status, have important prognostic roles for glioblastoma patients. The authors studied the efficacy and safety of stereotactic radiosurgery (SRS) for glioblastoma patients with consideration of molecular tumor profiles. METHODS:For this retrospective observational multiinstitutional study, the authors pooled consecutive patients who were treated using SRS for glioblastoma at eight institutions participating in the International Radiosurgery Research Foundation. They evaluated predictors of overall and progression-free survival with consideration of IDH mutation and MGMT methylation status. RESULTS:Ninety-six patients (median age 56 years) underwent SRS (median dose 15 Gy and median treatment volume 5.53 cm3) at 147 tumor sites (range 1 to 7). The majority of patients underwent prior fractionated radiation therapy (92%) and temozolomide chemotherapy (98%). Most patients were treated at recurrence (85%), and boost SRS was used for 12% of patients. The majority of patients harbored IDH wild-type (82%) and MGMT-methylated (62%) tumors. Molecular data were unavailable for 33 patients. Median survival durations after SRS were similar between patients harboring IDH wild-type tumors and those with IDH mutant tumors (9.0 months vs 11 months, respectively), as well as between those with MGMT-methylated tumors and those with MGMT-unmethylated tumors (9.8 vs. 9.0 months, respectively). Prescription dose > 15 Gy (OR 0.367, 95% CI 0.190-0.709, p = 0.003) and treatment volume > 5 cm3 (OR 1.036, 95% CI 1.007-1.065, p = 0.014) predicted overall survival after controlling for age and IDH status. Treatment volume > 5 cm3 (OR 2.215, 95% CI 1.159-4.234, p = 0.02) and absence of gross-total resection (OR 0.403, 95% CI 0.208-0.781, p = 0.007) were associated with inferior local control of SRS-treated lesions in multivariate models. Nine patients experienced adverse radiation events after SRS, and 7 patients developed radiation necrosis at 59 to 395 days after SRS. CONCLUSIONS:Post-SRS survival was similar as a function of IDH mutation and MGMT promoter methylation status, suggesting that molecular profiles of glioblastoma should be considered when selecting candidates for SRS. SRS prescription dose > 15 Gy and treatment volume ≤ 5 cm3 were associated with longer survival, independent of age and IDH status. Prior gross-total resection and smaller treatment volume were associated with superior local control.
PMID: 34740186
ISSN: 1933-0693
CID: 5038522

Commentary: Does Variceal Drainage Affect Arteriovenous Malformation Obliteration and Hemorrhage Rates After Stereotactic Radiosurgery? A Case-Matched Analysis [Comment]

Kondziolka, Douglas
PMID: 34293170
ISSN: 1524-4040
CID: 5039662

Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study

Burke, Rebecca M; Chen, Ching-Jen; Ding, Dale; Buell, Thomas J; Sokolowski, Jennifer; Sheehan, Kimball A; Lee, Cheng-Chia; Sheehan, Darrah E; Kano, Hideyuki; Kearns, Kathryn N; Tzeng, Shih-Wei; Yang, Huai-Che; Huang, Paul P; Kondziolka, Douglas; Ironside, Natasha; Mathieu, David; Iorio-Morin, Christian; Grills, Inga S; Feliciano, Caleb; Barnett, Gene; Starke, Robert M; Lunsford, L Dade; Sheehan, Jason P
BACKGROUND:Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. OBJECTIVE:To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. METHODS:We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). RESULTS:The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%,  < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013). CONCLUSION:Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role.
PMID: 34333653
ISSN: 1524-4040
CID: 5026552

Predicting local failure of brain metastases after stereotactic radiosurgery with radiomics on planning MR images and dose maps

Wang, Hesheng; Xue, Jinyu; Qu, Tanxia; Bernstein, Kenneth; Chen, Ting; Barbee, David; Silverman, Joshua S; Kondziolka, Douglas
PURPOSE/OBJECTIVE:Stereotactic radiosurgery (SRS) has become an important modality in the treatment of brain metastases. The purpose of this study is to investigate the potential of radiomic features from planning magnetic resonance (MR) images and dose maps to predict local failure after SRS for brain metastases. MATERIALS/METHODS/METHODS:Twenty-eight patients who received Gamma Knife (GK) radiosurgery for brain metastases were retrospectively reviewed in this IRB-approved study. 179 irradiated tumors included 42 that locally failed within one-year follow-up. Using SRS tumor volumes, radiomic features were calculated on T1-weighted contrast-enhanced MR images acquired for treatment planning and planned dose maps. 125 radiomic features regarding tumor shape, dose distribution, MR intensities and textures were extracted for each tumor. Logistic regression with automatic feature selection was built to predict tumor progression from local control after SRS. Feature selection and model evaluation using receiver operating characteristic (ROC) curves were performed in a nested cross validation (CV) scheme. The associations between selected radiomic features and treatment outcomes were statistically assessed by univariate analysis. RESULTS:The logistic model with feature selection achieved ROC AUC of 0.82 ± 0.09 on 5-fold CV, providing 83% sensitivity and 70% specificity for predicting local failure. A total of 10 radiomic features including 1 shape feature, 6 MR images and 3 dose distribution features were selected. These features were significantly associated with treatment outcomes (p < 0.05). The model was validated on independent holdout data with an AUC of 0.78. CONCLUSIONS:Radiomic features from planning MR images and dose maps provided prognostic information in SRS for brain metastases. A model built on the radiomic features shows promise for early prediction of tumor local failure after treatment, potentially aiding in personalized care for brain metastases.
PMID: 34287940
ISSN: 2473-4209
CID: 5003892

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study

Bunevicius, Adomas; Fribance, Sarah; Pikis, Stylianos; Lee, John Y K; Buch, Love Y; Moran, Michael; Yang, Andrew I; Bernstein, Kenneth; Mathieu, David; Perron, Rémi; Liscak, Roman; Simonova, Gabriela; Patel, Samir; Trifiletti, Daniel M; Martínez Álvarez, Roberto; Martínez Moreno, Nuria; Lee, Cheng-Chia; Yang, Huai-Che; Strickland, Ben A; Zada, Gabriel; Chang, Eric L; Kondziolka, Douglas; Sheehan, Jason
PMID: 33978475
ISSN: 1557-9077
CID: 4878392

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA

Kowalchuk, Roman O; Shepard, Matthew J; Sheehan, Kimball; Sheehan, Darrah; Faramand, Andrew; Niranjan, Ajay; Kano, Hideyuki; Gurewitz, Jason; Bernstein, Kenneth; Liscak, Roman; Guseynova, Khumar; Grills, Inga S; Parzen, Jacob S; Cifarelli, Christopher P; Rehman, Azeem A; Atik, Ahmet; Bakhsheshian, Joshua; Zada, Gabriel; Chang, Eric; Giannotta, Steven; Speckter, Herwin; Wu, Hsiu-Mei; Kondziolka, Douglas; Mathieu, David; Lee, Cheng-Chia; Warnick, Ronald E; Lunsford, L Dade; Trifiletti, Daniel M; Sheehan, Jason P
PURPOSE/OBJECTIVE:This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial. METHODS AND MATERIALS/METHODS:From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis. RESULTS:, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%). CONCLUSIONS:SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.
PMID: 33548341
ISSN: 1879-355x
CID: 4835422

Commentary: Developing a Professionalism and Harassment Policy for Organized Neurosurgery [Comment]

Kondziolka, Douglas; Markert, James M; McDermott, Michael; Robinson, Shenandoah; Connolly, E Sander
PMID: 33989409
ISSN: 1524-4040
CID: 4889412

Hippocampal sparing in patients receiving radiosurgery for ≥ 25 brain metastases

Kavi, Ami; Gurewitz, Jason; Benjamin, Carolina; Silverman, Joshua; Bernstein, Kenneth; Mureb, Monica; Oh, Cheongeun; Sulman, Erik P; Donahue, Bernadine; Kondziolka, Douglas
PURPOSE/OBJECTIVES/OBJECTIVE:To report our dosimetric analysis of the hippocampi (HC) and the incidence of perihippocampal tumor location in patients with≥25 brain metastases who received stereotactic radiosurgery (SRS) in single or multiple sessions. Materials/Methods Analysis of our prospective registry identified 89 patients treated with SRS for ≥ 25 brain metastases. HC avoidance regions (HA-region) were created on treatment planning MRIs by 5mm expansion of HC. Doses from each session were summed to calculate HC dose. The distribution of metastases relative to the HA-region and the HC was analyzed. RESULTS:Median number of tumors irradiated per patient was 33 (range 25-116) in a median of 3 (range1-12) sessions. Median bilateral HC Dmin (D100), D40, D50, Dmax, and Dmean (Gy) was 1.88, 3.94, 3.62, 16.6, and 3.97 for all patients, and 1.43, 2.99, 2.88, 5.64, and 3.07 for patients with tumors outside the HA-region. Multivariate linear regression showed that the median HC D40, D50, and Dmin were significantly correlated with the tumor number and tumor volume (p <0.001). Of the total3059 treated tumors,83 (2.7%) were located in the HA-region in 57% evaluable patients; 38 tumors (1.2%) abutted or involved the HC itself. CONCLUSIONS:Hippocampal dose, is higher in patients with tumors in the HA-region; however, even for patients with a high burden of intracranial disease and tumors located in the HA-regions, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half of our patients.
PMID: 34052342
ISSN: 1879-0887
CID: 4890712

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study

Shepard, Matthew J; Xu, Zhiyuan; Kearns, Kathryn; Li, Chelsea; Chatrath, Ajay; Sheehan, Kimball; Sheehan, Darrah; Faramand, Andrew; Niranjan, Ajay; Kano, Hideyuki; Gurewitz, Jason; Bernstein, Kenneth; Liscak, Roman; Guseynova, Khumar; Grills, Inga S; Parzen, Jacob S; Cifarelli, Christopher P; Rehman, Azeem A; Atik, Ahmet; Bakhsheshian, Joshua; Zada, Gabriel; Chang, Eric; Giannotta, Steven; Speckter, Herwin; Wu, Hsiu-Mei; Kondziolka, Douglas; Golfinos, John G; Mathieu, David; Lee, Cheng-Chia; Warnick, Ronald E; Lunsford, L Dade; Sheehan, Jason P
BACKGROUND:Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described. OBJECTIVE:To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs. METHODS:An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS:A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively. CONCLUSION/CONCLUSIONS:AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.
PMID: 33469655
ISSN: 1524-4040
CID: 4861842